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Module 19311 lessonsRxPrep 2023 HIV integrase inhibitor material, reconciled with NIH Adult, Adolescent, Pediatric, and Perinatal HIV Guidelines and current FDA labeling through August 2026

Integrase Strand Transfer Inhibitors

Connect integrase chemistry and strand transfer to bictegravir, dolutegravir, raltegravir, elvitegravir, and cabotegravir, then design around resistance, cations, long-acting delivery, toxicity, pregnancy, and virologic response.

01

Explain integrase processing and strand transfer using the viral DNA, host DNA, and catalytic metal complex.

02

Relate the metal-chelating INSTI pharmacophore to antiviral activity and gastrointestinal cation interactions.

03

Differentiate the resistance barriers and current clinical positioning of individual INSTIs.

04

Evaluate the complete bictegravir, emtricitabine, and tenofovir alafenamide regimen.

05

Use once-daily or twice-daily dolutegravir according to resistance and inducing interactions.

06

Apply the virologic, resistance, and HBV boundaries for dolutegravir plus lamivudine.

07

Differentiate raltegravir formulations, rifampin management, and muscle toxicity.

08

Represent elvitegravir with cobicistat as an approved but nonpreferred contemporary option.

09

Select, administer, bridge, and discontinue long-acting cabotegravir plus rilpivirine safely.

10

Build agent-specific cation counseling instead of using one class-wide timing rule.

11

Use current 2026 pregnancy guidance for bictegravir and dolutegravir.

12

Close every regimen with resistance-aware virologic and delivery monitoring.

193.01

Lesson

Trap the Strand-Transfer Complex

Integrase strand transfer inhibitors act after reverse transcription. Their metal-binding pharmacophore traps the viral DNA and integrase complex before host DNA can accept the viral strand.

What to learn
  • Integrase
  • Viral DNA
  • Magnesium
  • Strand transfer
  • Provirus
Catalytic complexTrap viral DNA before host insertion
01Processed viral DNAReady in nucleus

Carry this evidence forward.

02Integrase and MgActive site

Carry this evidence forward.

03INSTI bindingMetal coordination

Carry this evidence forward.

04No strand transferNo new provirus

Own the next clinical action.

Prepare viral DNA ends

After reverse transcription, integrase processes the ends of viral DNA and escorts the preintegration complex into the nucleus.

Coordinate catalytic metals

INSTIs contain a metal-binding pharmacophore that coordinates magnesium ions in the integrase active site. An adjacent hydrophobic region helps anchor the drug near viral DNA.

Block strand transfer

The drug stabilizes an unproductive integrase, viral DNA, and metal complex. Host DNA cannot accept the processed viral strand, so a new provirus is not formed.

Define the limit

INSTIs prevent new integration events. They do not remove proviral DNA that has already integrated, and they do not replace the activity of companion antiretrovirals.

Quick check

0 of 1 answered
01What is the direct molecular action of an INSTI?
Answer every question to submit.
193.02

Lesson

Use the Barrier Without Ignoring the Genotype

Bictegravir and dolutegravir have higher resistance barriers than raltegravir and elvitegravir, but prior INSTI failure and cabotegravir exposure can create clinically important cross-resistance.

What to learn
  • High barrier
  • Integrase genotype
  • Cross-resistance
  • CAB-LA
  • Cumulative history
Resistance architectureRead the full integrase history
01Prior INSTIIncluding CAB-LA

Carry this evidence forward.

02GenotypeMutation pathway

Carry this evidence forward.

03BarrierBIC and DTG

Carry this evidence forward.

04Active regimenProtect the anchor

Own the next clinical action.

Differentiate generations

Raltegravir and elvitegravir can fail through fewer resistance steps. Bictegravir and dolutegravir usually require more complex pathways, but high barrier does not mean universal activity.

Request integrase explicitly

Standard genotyping may focus on reverse transcriptase and protease. Add integrase testing after INSTI failure and whenever prior long-acting cabotegravir treatment or PrEP could shape susceptibility.

Test during drug pressure

Obtain resistance testing while the failing regimen is being taken or within 4 weeks after stopping when possible. Later testing may miss selected populations.

Respect CAB-LA breakthrough

Cabotegravir-selected mutations can compromise dolutegravir and bictegravir. Use a non-INSTI high-barrier regimen while awaiting genotype when HIV follows CAB-LA PrEP exposure.

Quick check

0 of 1 answered
01Which history most strongly requires an integrase genotype before relying on bictegravir or dolutegravir?
Answer every question to submit.
193.03

Lesson

Read Bictegravir as the Complete Biktarvy Regimen

Bictegravir is available only with emtricitabine and tenofovir alafenamide. Its high barrier, once-daily use, and current pregnancy status are strengths, but the companion drugs and interactions remain part of every decision.

What to learn
  • BIC
  • FTC
  • TAF
  • Complete regimen
  • High barrier
Complete regimenRead all of Biktarvy
01BICHigh-barrier INSTI

Carry this evidence forward.

02FTCHIV and HBV

Carry this evidence forward.

03TAFHIV and HBV

Carry this evidence forward.

04One complete planOnce daily

Own the next clinical action.

Position current initial therapy

BIC/FTC/TAF is recommended for most people starting ART when prior CAB-LA exposure does not create unresolved INSTI resistance concern.

Keep the product intact

Bictegravir is not separately available. Review HBV activity, kidney function, prior NRTI resistance, drug interactions, weight, and the consequences of stopping FTC and TAF.

Interpret serum creatinine

Bictegravir can inhibit tubular creatinine secretion and produce a small early stable rise without reducing true filtration. Progressive change or tubular findings require a full renal evaluation.

Reject strong induction

Rifampin is contraindicated with Biktarvy. Review anticonvulsants, rifamycins, and herbal inducers before treatment and use a supported alternative rather than an improvised dose increase.

Quick check

0 of 1 answered
01What is the best interpretation of a small stable creatinine rise soon after starting Biktarvy with no other kidney abnormalities?
Answer every question to submit.
193.04

Lesson

Make Dolutegravir Frequency Evidence-Based

Dolutegravir is a high-barrier INSTI used in several complete regimens. Once-daily dosing is common, while selected inducers and resistance patterns require twice-daily exposure.

What to learn
  • Dolutegravir
  • UGT1A1
  • CYP3A
  • Twice daily
  • Hypersensitivity
Exposure and resistanceMake frequency evidence-based
01GenotypeINSTI pathway

Carry this evidence forward.

02InducersUGT1A1 and CYP3A

Carry this evidence forward.

03Once or twice dailyExact context

Carry this evidence forward.

04ResponseHIV RNA

Own the next clinical action.

Use once daily when appropriate

Dolutegravir 50 mg once daily is used for most treatment-naive or INSTI-naive adults without a clinically important inducer.

Know why frequency changes

Rifampin and selected UGT1A1 or CYP3A inducers can require 50 mg twice daily. Certain raltegravir or elvitegravir resistance patterns can also require twice-daily dosing when the isolate remains susceptible.

Do not dose through all resistance

Mutation pattern and companion activity determine whether increased exposure remains useful. Resistance consultation replaces automatic dose escalation after INSTI failure.

Act on hypersensitivity

Severe rash with constitutional symptoms or organ dysfunction, including liver injury, requires immediate discontinuation and evaluation. Do not rechallenge after a compatible serious reaction.

Quick check

0 of 1 answered
01Why might dolutegravir be prescribed twice daily?
Answer every question to submit.
193.05

Lesson

Use Dolutegravir Plus Lamivudine Inside Its Boundaries

DTG/3TC is a recommended two-drug regimen for selected patients, not a default rapid-start shortcut. Viral load, HBV, resistance, and CAB-LA history determine whether it is complete therapy.

What to learn
  • DTG/3TC
  • HIV RNA
  • HBV
  • 3TC susceptibility
  • Rapid start
Two-drug boundaryRequire the missing information
01RNA at most 500,000Initial limit

Carry this evidence forward.

023TC susceptibleGenotype available

Carry this evidence forward.

03No untreated HBVFull HBV plan

Carry this evidence forward.

04CAB history clearINSTI genotype if exposed

Own the next clinical action.

Apply the viral-load limit

Do not use DTG/3TC as initial therapy when baseline HIV RNA exceeds 500,000 copies/mL.

Protect HBV

DTG has no HBV activity and lamivudine alone has a low HBV resistance barrier. HBV coinfection requires tenofovir or another fully suppressive HBV plan.

Wait for essential tests

Before initial use, confirm HBV status and a reverse-transcriptase genotype showing lamivudine susceptibility. It is not the regimen for information-free rapid initiation.

Account for CAB-LA

If prior long-acting cabotegravir PrEP exposure exists, require documented INSTI susceptibility before using an INSTI-based initial regimen.

Quick check

0 of 1 answered
01Which patient should not begin DTG/3TC as initial therapy?
Answer every question to submit.
193.06

Lesson

Separate Raltegravir Formulations and Current Role

Raltegravir remains an effective approved INSTI, but formulation, rifampin, muscle toxicity, lower resistance barrier, and pill burden distinguish it from preferred contemporary initial anchors.

What to learn
  • Isentress
  • Isentress HD
  • Rifampin
  • CPK
  • Lower barrier
Formulation precisionDo not interchange the schedules
01Isentress400 mg twice daily

Carry this evidence forward.

02Isentress HD1,200 mg daily

Carry this evidence forward.

03RifampinHD not used

Carry this evidence forward.

04Muscle safetyCPK and symptoms

Own the next clinical action.

Do not interchange formulations

Isentress 400 mg twice daily and Isentress HD 1,200 mg once daily have different pharmacokinetic instructions. Tablet strengths are not substituted milligram for milligram.

Manage rifampin by formulation

With rifampin, use raltegravir 800 mg twice daily from the 400 mg formulation when appropriate. Isentress HD is not recommended with rifampin.

Investigate muscle symptoms

Raltegravir can elevate CPK and cause myopathy or rhabdomyolysis. Assess pain, weakness, dark urine, kidney function, exercise, trauma, statins, and other myotoxins.

Position it accurately

Raltegravir is no longer recommended for routine initial therapy because bictegravir and dolutegravir offer greater resistance barrier and convenience. Use it for a documented patient-specific reason.

Quick check

0 of 1 answered
01Which raltegravir plan is appropriate with rifampin when raltegravir is selected?
Answer every question to submit.
193.07

Lesson

Place Elvitegravir With Cobicistat in Modern Practice

Elvitegravir is available only in Genvoya and Stribild with cobicistat, FTC, and TAF or TDF. Its booster, food, renal, and interaction constraints make it nonpreferred for routine initial therapy.

What to learn
  • EVG/c
  • Cobicistat
  • Food
  • Genvoya
  • Stribild
Boosted legacy optionAccount for cobicistat and food
01EVGINSTI

Carry this evidence forward.

02COBIInteraction driver

Carry this evidence forward.

03FTC plus TAF or TDFComplete regimen

Carry this evidence forward.

04Current positionApproved, nonpreferred

Own the next clinical action.

Name every component

Cobicistat is required to maintain elvitegravir exposure and creates a broad CYP3A and transporter interaction network. FTC and TAF or TDF add HBV and renal considerations.

Use food

Both Genvoya and Stribild are taken once daily with food. This differs from bictegravir and dolutegravir products that generally do not require food.

Apply product-specific renal rules

Stribild contains TDF and has stricter creatinine-clearance restrictions. Use current product labeling rather than an old class-wide threshold.

Modernize the formulary

EVG/c regimens remain approved, but current NIH guidance no longer recommends them for routine initial therapy because BIC and DTG provide higher barriers and fewer interaction constraints.

Quick check

0 of 1 answered
01Why does an elvitegravir regimen have more interaction burden than bictegravir?
Answer every question to submit.
193.08

Lesson

Treat Long-Acting Cabotegravir as a Care System

Cabotegravir plus rilpivirine injections replace a suppressive oral regimen in selected patients. Eligibility, injection scheduling, oral bridging, and the prolonged pharmacologic tail are inseparable.

What to learn
  • CAB/RPV
  • Viral suppression
  • Optional lead-in
  • Gluteal IM
  • Pharmacologic tail
Long-acting careBuild the system around every injection
01EligibilitySuppressed and susceptible

Carry this evidence forward.

02InitiationLead-in optional

Carry this evidence forward.

03Target datesMonthly or every 2 months

Carry this evidence forward.

04Tail protectionBridge or replace

Own the next clinical action.

Confirm standard eligibility

Current guidance generally requires suppression for at least 3 months, no known or suspected CAB or RPV resistance, no active HBV unless separately treated, no pregnancy or active pregnancy planning, and no major interactions.

Individualize oral lead-in

Oral cabotegravir plus rilpivirine for at least 28 days is optional. Direct-to-injection use is supported when patient and clinician prefer it.

Use the selected schedule exactly

Monthly and every-2-month regimens use different initiation and continuation kits. Give separate cabotegravir and rilpivirine gluteal injections during the same visit and follow the target-date window.

Protect the long tail

Drug concentrations can persist for a year or longer. Planned delays may require oral bridging, prolonged delays may require re-initiation, and discontinuation requires fully suppressive alternative ART no later than 1 month after the final injections.

Quick check

0 of 1 answered
01What is the most dangerous CAB/RPV discontinuation error?
Answer every question to submit.
193.09

Lesson

Engineer Cation Timing by Agent and Product

Oral INSTIs can chelate aluminum, magnesium, calcium, iron, zinc, and other polyvalent cations. Exact management differs by agent, cation, food, antacid, supplement, and formulation.

What to learn
  • Chelation
  • Antacid
  • Supplement
  • Food
  • Timing
Absorption chemistryPrevent a chelation failure
01Find mineralsAntacid or supplement

Carry this evidence forward.

02Name the INSTIRules differ

Carry this evidence forward.

03Use food and timingRepeatable schedule

Carry this evidence forward.

04Verify exposureHIV RNA

Own the next clinical action.

Find hidden cations

Review antacids, multivitamins, prenatal vitamins, iron, calcium, magnesium, zinc, sucralfate, and mineral-containing laxatives. The mechanism is complex formation, not gastric pH.

Manage bictegravir precisely

Calcium or iron can be taken with bictegravir when both are taken with food. Avoid simultaneous fasting administration and apply separate aluminum or magnesium antacid timing.

Manage dolutegravir precisely

Calcium or iron can be taken with dolutegravir and food, or dolutegravir can be taken at least 2 hours before or 6 hours after the supplement. Aluminum and magnesium antacids require separation.

Respect raltegravir exceptions

Do not coadminister aluminum or magnesium hydroxide antacids with raltegravir. Timing does not reliably repair every combination, and calcium guidance differs by formulation.

Quick check

0 of 1 answered
01How can calcium or iron be taken with dolutegravir?
Answer every question to submit.
193.10

Lesson

Interpret Creatinine, Weight, Mood, Muscle, and Pregnancy

INSTI safety is generally favorable, but agent-specific transporter, metabolic, neuropsychiatric, muscle, hepatic, and hypersensitivity effects require longitudinal interpretation.

What to learn
  • Creatinine secretion
  • Weight
  • Mood
  • Muscle
  • Pregnancy
Longitudinal interpretationClassify the signal before acting
01CreatinineSecretion or injury

Carry this evidence forward.

02Weight and moodTrend and context

Carry this evidence forward.

03Muscle and liverAgent specific

Carry this evidence forward.

04PregnancyBIC and DTG preferred

Own the next clinical action.

Separate secretion from kidney injury

Bictegravir and dolutegravir can raise serum creatinine without reducing true GFR. Progressive decline, proteinuria, glucosuria, phosphate loss, or symptoms require a broader assessment.

Interpret weight over time

Weight gain has been observed with INSTI-based therapy and may be greater with TAF-containing regimens and in selected populations. Evaluate return to health, diet, activity, endocrine disease, and alternatives without overstating a single cause.

Screen mood and muscle symptoms

Insomnia and mood symptoms can occur, especially with preexisting psychiatric risk. Raltegravir has a stronger CPK and muscle-injury signal. Investigate suicidality or rhabdomyolysis urgently.

Use current pregnancy evidence

The early neural-tube-defect concern for dolutegravir is no longer the current clinical frame. March 2026 perinatal guidance lists both bictegravir and dolutegravir as preferred INSTIs in pregnancy, with no BIC dose adjustment recommended.

Quick check

0 of 1 answered
01Which statement reflects current U.S. perinatal guidance?
Answer every question to submit.
193.11

Lesson

Build One Accountable INSTI Regimen

The final choice joins resistance, companion activity, HBV, organs, cations, inducers, pregnancy, route, access, and monitoring. The anchor cannot be separated from the complete regimen or delivery system.

What to learn
  • Complete ART
  • Genotype
  • HBV
  • Delivery
  • HIV RNA
Clinical synthesisAlign virus, regimen, person, and delivery
01ResistanceIncluding integrase

Carry this evidence forward.

02Complete ARTHBV and companions

Carry this evidence forward.

03FeasibilityCations and access

Carry this evidence forward.

04Follow-upRNA and ownership

Own the next clinical action.

Start with viral evidence

Review cumulative resistance, prior INSTI exposure, and CAB-LA treatment or PrEP. Obtain integrase testing when indicated and do not assume high barrier overcomes cross-resistance.

Fit every regimen component

Confirm HBV treatment, kidney and liver function, pregnancy, cations, inducers, fixed-dose components, food, route, and access before final selection.

Verify early suppression

If suppression is not achieved in 8 to 12 weeks, reassess adherence, mineral timing, inducers, dispensing, companion activity, and genotype including integrase.

Own long-acting continuity

For CAB/RPV, assign target-date tracking, recall, oral bridge access, an alternate injection pathway, and a rapid transition plan if treatment stops.

Quick check

0 of 1 answered
01Which INSTI selection process is most complete?
Answer every question to submit.

Module test

Check the connections.

Each attempt draws 10 questions from the complete 156 question bank.

156 questions in this module bank10 questions per attempt

Each attempt draws a fresh set and rearranges the answer choices.

References

Current clinical foundation.

Lecture material was synthesized with the following contemporary guidance. Verify local policy and current guidance before applying clinical information.

  1. NIH Integrase Inhibitor Characteristics
  2. NIH Initial Integrase Inhibitor Regimens
  3. NIH Initial Combination Regimens
  4. NIH Integrase Inhibitor Drug Interactions
  5. NIH Long-Acting CAB/RPV Optimization
  6. NIH Drug Resistance Testing
  7. NIH Initial ART During Pregnancy
  8. FDA Biktarvy Prescribing Information
  9. FDA Tivicay Prescribing Information
  10. FDA Cabenuva Prescribing Information
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